Among the multiple autoantibodies identified in the serum of systemic sclerosis (SSc) patients, three are disease-specific, mutually exclusive, and helpful to determine the prognosis: anticentromere antibodies, antitopoisomerase 1 antibodies (ATA), and anti-RNA-polymerase III antibodies. ATA can be identified through different techniques, including double immunodiffusion (DID) assay, enzyme-linked immunosorbent assay (ELISA), or immunoblot. Although all of them are commonly used, none of them can be considered as the reference. Herein, we propose a brief description of the different methods available for the detection of ATA. All these studies revealed that ATA, determined by DID assay, ELISA, or immunoblot, are highly specific for SSc although the reported sensitivity is fickle. As we recently reported, patients with ATA had an almost similar phenotype without distinction between the methods of detection, ELISA, and immunoblot, and the use of these two techniques improves the sensitivity without diminishing the specificity. Thus, we may propose that a combination of the immunoblot using HEp-2 cells antigens and ELISA could be used for the detection of ATA.